rs4262642

chr10-128047283-A-Cchr10-128047283-A-Gchr10-128047283-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006504.6(PTPRE):c.110-107A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,433,764 control chromosomes in the GnomAD database, including 434,401 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46086 hom., cov: 33)
  • Exomes 𝑓: 0.78 (388315 hom.)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

Genes affected

PTPRE (HGNC:9669): (protein tyrosine phosphatase receptor type E) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Several alternatively spliced transcript variants of this gene have been reported, at least two of which encode a receptor-type PTP that possesses a short extracellular domain, a single transmembrane region, and two tandem intracytoplasmic catalytic domains; another one encodes a PTP that contains a distinct hydrophilic N-terminus, and thus represents a nonreceptor-type isoform of this PTP. Studies of the similar gene in mice suggested the regulatory roles of this PTP in RAS related signal transduction pathways, cytokine-induced SATA signaling, as well as the activation of voltage-gated K+ channels. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRE	NM_006504.6	c.110-107A>C		intron_variant		ENST00000254667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRE	ENST00000254667.8	c.110-107A>C		intron_variant		1	NM_006504.6
PTPRE	ENST00000442830.5	c.110-107A>C		intron_variant		5
PTPRE	ENST00000455661.5	c.110-107A>C		intron_variant		2
PTPRE	ENST00000471218.5	c.110-107A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118101 AN: 152034 Hom.: 46058 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.778 AC: 997135 AN: 1281612 Hom.: 388315 AF XY: 0.778 AC XY: 486639 AN XY: 625790

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.849

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.767

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.772

GnomAD4 genome AF: 0.777 AC: 118183 AN: 152152 Hom.: 46086 Cov.: 33 AF XY: 0.776 AC XY: 57726 AN XY: 74378

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.750

Alfa AF: 0.778 Hom.: 85734

Bravo AF: 0.782

Asia WGS AF: 0.821 AC: 2855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4262642; hg19: chr10-129845547;